Most Common Side Effects of Hydralazine
The most common side effects of hydralazine are headache, gastrointestinal complaints (nausea, vomiting), tachycardia, flushing, and hypotension, with headache and GI symptoms being so frequent that many patients cannot continue treatment at target doses. 1
Primary Cardiovascular Side Effects
Reflex Tachycardia and Hemodynamic Changes
- Hydralazine causes reflex tachycardia due to increased sympathetic tone as a compensatory response to arterial vasodilation. 1, 2
- Palpitations and dizziness commonly occur alongside the tachycardia. 1, 3
- Hypotension and postural hypotension may develop, though less common than with other antihypertensive classes. 1, 3
- Flushing is frequently reported due to the vasodilatory effects. 1
Cardiac Ischemia Risk
- Myocardial stimulation from hydralazine can provoke anginal attacks and ECG changes consistent with myocardial ischemia, and has been implicated in causing myocardial infarction. 3
- This risk necessitates extreme caution in patients with suspected coronary artery disease. 3
Gastrointestinal and Systemic Effects
Common GI Complaints
- Headache and gastrointestinal complaints (including nausea and vomiting) are so prevalent that they represent the primary reason for treatment discontinuation at target doses. 1
- These side effects occur frequently enough to significantly impact medication compliance. 1
Fluid Retention
Neurological Side Effects
- Peripheral neuritis manifesting as paresthesia, numbness, and tingling has been observed. 3
- This appears related to an antipyridoxine effect, and pyridoxine supplementation should be added if symptoms develop. 3
Immunologic Reactions (Dose-Dependent)
Drug-Induced Lupus-Like Syndrome
- A lupus-like syndrome is the most common immunologic side effect, particularly at higher doses, which is why total daily doses should be kept below 150 mg. 1, 2, 3
- Symptoms include arthralgia, fever, chest pain, and continued malaise. 3
- This requires monitoring with complete blood counts and antinuclear antibody titers before and periodically during prolonged therapy. 3
Hematologic Effects
- Blood dyscrasias including reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, and purpura have been reported. 3
- Hemolytic anemia, vasculitis, and glomerulonephritis are less common but serious adverse effects. 4
Clinical Context and Tolerability
The high incidence of adverse reactions with hydralazine has led to generally poor compliance, particularly when multiple daily doses are required. 1 This tolerability profile explains why hydralazine has largely been replaced by newer antihypertensive agents in developed countries, though it remains widely used in developing nations due to lower cost. 4
The side effect profile is both dose-dependent and duration-dependent, with acetylator status also playing a role in individual susceptibility. 5